Significance of Loss of Heterozygosities in Predicting Sentinel Lymph Node Metastasis of Breast Invasive Ductal Carcinoma
B Zhu, SD Finkelstein, R Saad, JF Silverman, X Lin. Northwestern University, Chicago, IL; RedPath Integrated Pathology, Inc., Pittsburgh, PA; Allegheny General Hospital, Pittsburgh, PA
Background: Sentinel lymph node (SLN) metastasis of breast invasive ductal cancer (BIDC) is one of the main criteria determining stage that is the strongest predictor of disease aggressiveness and survival, and determining the need for axillary resection and additional therapy. We studied SLN metastasis using a combined histopathologic/molecular approach to gain insights into the pathobiology implications.
Design: Fourteen BIDC patients with positive SLN and 19 with negative SLN were retrieved. Analysis of 17 polymorphic microsatellite repeat markers targeting 1p34-36, 3p24-26, 5q23, 9p21, 10q23, 17p13, 17q12, 17q21, 21q22, and 22q13 was performed in DNA isolated from primary tumors and metastatic tumors.
Results: BIDCs with SLN metastasis showed larger size (p=0.004) and higher nuclear grade (P=0.047) than those with negative SLN, which correlated with higher fractional mutation rate (FMR) of the primary tumor and shared FMR by the primary and SLN tumors. SLN metastasis was not related with expression of estrogen receptor, progesterone receptor, and Her2/neu, and did not correlate with higher FMR. However, higher FMR was related to higher percentage of positive SLNs. Tumor size is not necessarily a strong marker for the prediction of aggressiveness and metastasis of BDC, indicting that some smaller BIDCs arise intrinsically as an aggressive malignancy with metastatic disease. LOHs at 1p34-36, 3p24-26, 9p21, 10q23, 17p13, 17q12, 21q22 and 22q13 may play an important role in the development and aggressiveness of BIDC. LOHs at 1p34-36, 17p13 and 22q13 may play an important role in metastasis. None of the LOHs were shared by all the tumors, suggesting that BIDC develops using various pathways that have unique and personalized patterns of mutational changes.
Conclusions: Detection of LOH is useful in studying oncogenesis and predicting aggressiveness and metastasis of BIDC.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 228, Monday Morning